Liposome immunoadjuvants containing IL-2

Abstract

The present invention provides a liposome comprising an effective immunoadjuvant amount of a lymphokine such as IL-2. Also provided is an effective antineoplastic amount of IL-2 liposomes in combination with adoptively transferred cells stimulated with anti-CD3 monoclonal antibody plus IL-2.

What is claimed is: 
     
       1. A method of increasing the immunoadjuvant efficacy of interleukin-2 (IL-2) in an in vivo treatment protocol in which IL-2 is used as an immunoadjuvant, said method comprising: (a) incorporating an effective immunoadjuvant amount of IL-2 into liposomes to produce IL-2-containing liposomes, without the use of an organic solvent, by: (i) hydrating a single powdered lipid, said lipid being dimyristoyl phosphatidyl choline (DMPC), with an aqueous IL-2 solution to produce an aqueous IL-2/DMPC mixture; in which at least about 31% of the IL-2 in said aqueous IL-2 solution is encapsulated in said IL-2 -containing liposomes; and       (b) administering said IL-2-containing liposomes to a patient.   
     
     
       2. The method of claim 1 wherein said step of incorporating IL-2 into liposomes includes the steps of sonicating, freezing, and thawing said aqueous IL-2/lipid mixture to produce IL-2-containing liposomes. 
     
     
       3. The method of claim 1 wherein said step of incorporating IL-2 into liposomes includes a step of hydrating a single powdered lipid with a sufficient amount of aqueous IL-2 solution such that the concentration of lipid in said aqueous IL-lipid mixture is about 300 mg/ml. 
     
     
       4. The method of claim 3 wherein at least about 70% of the IL-2 in said aqueous IL-2 solution is encapsulated by the liposomes. 
     
     
       5. The method of claim 4 wherein said step of incorporating IL-2 into liposomes includes the steps of sonicating, freezing, and thawing said aqueous IL-2/lipid mixture to produce IL-2-containing liposomes. 
     
     
       6. The method of claim 5 wherein at least about of the IL-2 in said aqueous IL-2 solution is encapsulated by the liposomes. 
     
     
       7. A method of increasing the antineoplastic efficacy of interleukin-2 (IL-2) in an in vivo treatment protocol in which IL-2 is used as an antineoplastic agent, said method comprising: (a) incorporating an effective antineoplastic amount of IL-2 into liposomes to produce IL-2-containing liposomes, without the use of an organic solvent, by: (i) hydrating a single powdered lipid, said lipid being dimyristoyl phosphatidyl choline (DMPC), with an aqueous IL-2 solution to produce an aqueous IL-2/DMPC mixture; in which at least about 31% of the IL-2 in said aqueous IL-2 solution is encapsulated in said IL-2containing liposomes; and       (b) administering said IL-2-containing liposomes to a patient.   
     
     
       8. The method of claim 7 wherein said step of incorporating IL-2 into liposomes includes the steps of sonicating, freezing, and thawing said aqueous IL-2/lipid mixture to produce IL-2-containing liposomes. 
     
     
       9. The method of claim 7 wherein said step of incorporating IL-2 into liposomes includes a step of hydrating a single powdered lipid with a sufficient amount of aqueous IL-2 solution such that the concentration of lipid in said aqueous IL-2/lipid mixture is about 300 mg/ml. 
     
     
       10. The method of claim 9 wherein at least about 70% of the IL-2 in said aqueous IL-2 solution is encapsulated by the liposomes. 
     
     
       11. The method of claim 9 wherein said step of incorporating IL-2 into liposomes includes the steps of sonicating, freezing, and thawing said aqueous IL-2/lipid mixture to produce IL-2-containing liposomes. 
     
     
       12. The method of claim 11 wherein at least about 90% of the IL-2 in said aqueous IL-2 solution is encapsulated by the liposomes. 
     
     
       13. The method of claim 7 wherein the antineoplastic efficacy is increased for pulmonary metastases. 
     
     
       14. The method of claim 5 wherein the IL-2 in liposomes is administered intrathoracically.